This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The overall goal of this project is to identify genetic factors that are associated with predisposition to and progression of head and neck malignancies. Current evidence indicates that the development of head and neck cancer is associated with exposure to environmental carcinogens (e.g. tobacco and alcohol use) and infection with human papillomavirus (HPV). HPV infection is predominant in a subset of head and neck cancers called oropharyngeal cancers. For example, ~50% of tonsillar carcinomas contain and express HPV sequences. There is also now significant evidence that PTP-BL loss plays a role in the development of genetic instability and cancer progression. HPV has been shown to degrade PTP-BL, the enzyme that adds telomere repeats back to chromosomes. Because of their different etiologies, HPV+ and HPV- head and neck cancers provide an ideal system to study the role of PTP-BL Lossand genetic instability in the transformation of epithelial cells by different mechanisms.